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Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer

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Abstract

Background

Early and accurate detection of adenomatous colonic polyps is a major concern in the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging with optical probes targeting specific peptides enables the noninvasive visualization and characterization of lesions. Matrix metalloproteinases (MMPs) are known to play an important role in tumorigenesis and tumor progression.

Aim

To investigate the effectiveness of NIRF imaging, with a novel MMP-activatable probe based on a polymeric nanoparticle platform, in the colon cancer models.

Methods

We used an azoxymethane (AOM)-induced mouse colon cancer model resembling human sporadic colon cancer and an MMP-positive xenograft tumor model. MMP expression was evaluated by Western blotting, real-time PCR, and immunohistochemical staining. NIRF imaging was performed with a novel MMP-activatable probe, an MMP-inactivatable probe, and saline. In addition, we observed the change of NIRF signal intensity after intratumoral administration of an MMP-inhibitor.

Results

Multiple tumors with various sizes developed in AOM-treated mouse colons, progressing from adenomas to adenocarcinomas, with MMP expression progressively increasing in the normal-adenoma-adenocarcinoma sequence. In mice injected with the MMP-activatable probe, the NIRF signal also increased in this sequence and was highly correlated with MMP expression (p < 0.001). Tumor-background-ratios (TBR) of adenocarcinoma to adjacent normal mucosa by a novel probe were significantly higher than that of adenoma (p < 0.001). In both the AOM and xenograft models, NIRF signals of tumors decreased after treatment with an MMP-inhibitor.

Conclusions

NIRF imaging using a polymeric nanoparticle-based probe may be useful for detecting early stage disease and for assessing treatment response.

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Acknowledgments

This work was supported by grants from the Korea Health 21 R&D project, the Ministry for Health, Welfare, and Family, Republic of Korea (A062254), the Asan Institute for Life Sciences (2008-261), and the Korean Association for the Study of Intestinal Diseases.

Conflict of interest

The authors have no financial interest or affiliation with any commercial supporter or providers of any commercial services. The authors alone are responsible for the content and writing of this paper.

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Authors and Affiliations

  1. Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea

    Soon Man Yoon

  2. Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, Seoul, 138-736, Korea

    Seung-Jae Myung, Byong Duk Ye, Dong-Hoon Yang, Kyoung Jo Kim, Jeong-Sik Byeon, Suk-Kyun Yang & Jin-Ho Kim

  3. Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea

    Seung-Jae Myung, In-Wha Kim, Eun-Ju Do, Byong Duk Ye & Dae Hyuk Moon

  4. Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea

    Ju Hee Ryu, Kyeongsoon Park, Kwangmeyung Kim & Ick Chan Kwon

  5. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Mi Jung Kim

  6. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Dae Hyuk Moon

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  1. Soon Man Yoon
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Correspondence to Seung-Jae Myung.

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Yoon, S.M., Myung, SJ., Kim, IW. et al. Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer. Dig Dis Sci 56, 3005–3013 (2011). https://doi.org/10.1007/s10620-011-1685-z

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  • DOI: https://doi.org/10.1007/s10620-011-1685-z

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